CONTRACEPTION IN HIV INFECTION DR JYOTI DHAR LEICESTER UK

Transcription

1 CONTRACEPTION IN HIV INFECTION DR JYOTI DHAR LEICESTER UK

2 Global figures Women account for 51.6% of HIV globally (15.9m of 30.8m HIV+ adults) UNAIDS report on the global AIDS epidemic, 2010

3 Estimated no. PLWH: UK, 2012 HIV in the United Kingdom: 2012 Overview, HIV and STI Department, Health Protection Agency. Available at

4 Female issues Pregnancy-related Prevention Safe conception, pregnancy & delivery Health Bone mineral density Breast & cervical health & screening HIV-related Risk & progression ARV Efficacy & PK Tolerability & toxicity Social Stigma Autonomy Responsibility

5 By Region for the same time period (%) Developing Countries Latin America / Caribbean Asia Sub-Saharan Africa

6 Contraception and HIV More than 80% of all women living with HIV are in their reproductive years Many will continue to want children after learning of their positive status and others will choose to regulate their fertility

7 ACKNOWLEDGE THAT A POSITIVE WOMAN MAY WANT TO CONTROL HER FERTILITY : SUPPORT THE CHOICE ACCESS TO EFFECTIVE CONTRACEPTION TO PREVENT UNDESIRED PREGNANCY AVOID A CASE OF PERINATAL HIV INFECTION AND MATERNAL MORTALITY DISCUSSION ABOUT HORMONAL CONTRACEPTION IS PIVOTAL TO PREVENT UNPLANNED PREGNANCY MTCT MODEL : INCREASING CONTRACEPTIVE USE WILL PREVENT 28.6% MORE HIV BIRTHS THAN USE OF PERIPARTUM NVP IN THE ERA OF EFFECTIVE ARVS HIV INFECTION HAS IMPLICATIONS FOR CONTRACEPTION

8 IMPACT OF GENDER ON HIV

9 Potential gender differences BARRIERS TO ADHERENCE e.g.. cultural, behavioural PHARMACOLOGICAL e.g.. pharmacokinetic PSYCHOLOGICAL e.g.. risk of depression d'arminio Monforte A. AIDS 2010; 24(8):

10 Possible differences in PK parameters relevant to ARVs Pharmacokinetics Bioavailability Distribution Metabolism Elimination acid, slower gastric emptying (OCP, preg) Diet differences No consistent differences in gut CYP or p-gp Lower weight More % fat Varying plasma volumes Less organ flow Oestrogen has effects on plasma binding proteins In vitro: F>M trend Progesterone CYP3A4 activity Hepatic p-gp M>F Smaller organs HepC and liver status Administration of concomitant medications can affect each stage Gandhi Annu Rev Pharm Tox 2004; Mirfazaellan EJ Clin Pharm 2002; Wobold Hepatol 2003

11 Aims Factors affecting an HIV positive women s contraceptive choices relevant guidelines Case: To review and highlight some female specific issues related to HIV & ART To review complications & important drug-drug interactions

12 Questions for you to consider? Will a woman: Show that she knows her contraception well She be able to tell her male counterpart that she is bothered about her health and so should he She go ahead and bring condoms for him to use She be respected for her interest in use of condoms Expecting a man to make balanced choices keeping the female in mind is a bit too far

13 Access to Quality of care Every woman is an individual and brings to a consultation physical, pshycosocial factors that need to be assesed before recommending contraception Clinicians provide environment and responsive to these challenges

14 GUIDELINES

15 There are no evidence based guidelines for this group of people So current best practice is based on Evidence based guidance from FFPRHC UK medical eligibility criteria for contraceptive use (UKMEC) UK guidelines for management of sexual and reproductive health of people living with HIV

16 UKMEC categories An adaptation for UK practice, of WHO medical eligibility criteria. 4 categories. UKMEC category Definition of category 1 Unrestricted use of the method 2 Benefits of the method outweigh the risks 3 Risks outweigh the benefits 4 Unacceptable health risk

17 BHIVA ART Guidelines 2013: NEW women s section We recommend that potential PK interactions between ARVs, hormonal contraceptive agents and HRT are checked prior to administration BHIVA guidelines for the treatment of HIV-1 positive adults with antiretroviral therapy 2012, 30 th April 2012; Accessed at on 4 th May 2012

18 Case review: Zara 31 year old female known HIV positive, not on ARVs attends requesting contraception Feb 2010 Diagnosed 2 yrs ago following Pulmonary TB diagnosis RMP of 1 year HIV-negative CD4 520 (38%), VL 34,000, R test WT No evidence to suggest reduced safety or efficacy of any hormonal methods used in ARV naïve women UKMEC Category 1

19 Barrier methods

20 Condom Facts Male condoms are an effective barrier to the passage of bacteria, viruses and semen. They are up to 98% effective in preventing pregnancy. Consistent use for each episode of vaginal intercourse in sero discordant couples reduces HIV transmission by at least 80%.

21 Condom Facts The use of a stronger (thicker) condom instead of standard condoms does not reduce the risk of breakage and is not generally recommended.

22 Condoms with spermicides The use of condoms lubricated with spermicide is not recommended. Currently available spermicides do not provide protection against HIV Spermicides in condoms have a potential irritant effect on mucosa and do not provide additional protection against pregnancy.

23 Polyurethane Marketed as: Stronger than latex Deteriorates slower? Transmits more body heat No odour Resists oil-based lubricants In trials have been shown to have similar efficacy to latex

24 Female Condom Consists of a polyurethane sheath with a flexible ring at each end. The upper ring is placed in the upper vagina and the lower ring covers the introitus Laboratory evidence suggests that female condoms also protect against STIs

25 Case review: Zara Declines starting ARVs Mar 2012: CD4 440 (25%), VL 66,000 Jun 2012: CD4 370 (22%), VL 89,500 Decides to commence ART and Requests One tablet regimen Attends with partner split condom the night before

26 Case review: Zara would you recommend PEP to negative partner? would you recommend Emergency contraception?

27 'Morning-after' pills for HIV?

28 Emergency contraception options - Zara Copper IUD is the preferred method Highly effective Unaffected by liver enzyme inducers doubling the dose to 3mg stat is recommended if on ARVs Ella- one not recommended

29 Case review: Zara Condoms offer less contraceptive efficacy she wants to choose another method

30 Case review: Zara Condoms may offer less contraceptive efficacy If she chooses another method? Will some contraceptive methods alter her disease progression? Will her infectivity (HIV genital shedding) be altered with certain types of contraception?

31 Will some contraceptive methods alter her disease progression? Limited evidence on the effect. There appears to be no significant effect on CD4 lymphocyte count or viral load

32 Hormonal contraceptives- infectivity Conflicting studies HIV Transmission HIV genital shedding Cervical ectopy Irregular/heavy periods Kenyan study Rapid CD4 decline on OC commencement studies (pts not on ARVs) HIV Acquisition No association with the pill Potential association Use of DMPA (depo) times risk

33 Controversies around DMPA -Depo Recent WHO review: Enough concern regarding acquisition to recommend condoms to protect against HIV negative women on DMPA Women living with HIV can continue to use all existing hormonal contraceptive methods.condoms, male or female, are critical for prevention of HIV transmission WHO: Hormonal contraception and HIV, Technical statement; 16 February Accessed at

34 Hormonal Contraception and use of Antiretroviral therapy Questions: Is there decreased contraceptive efficacy? Is there decreased efficacy of ART? Are there increased side effects related to either the hormonal contraception or the ART

35 IMPACT OF CONTRACEPTION ON ART

36 Hormonal Contraceptive Methods amongst the most widely used worldwide Combined oral contraceptive pill (COC) The combined contraceptive patch The progestogen only pill Injectable progestogens The progestogen implant

37 Combined oral contraceptive pill Contains 20-30micrograms of ethinyl oestrodiol in combination with a progestogen High contraceptive efficacy o Perfect use 0.1% failure rate o Typical use up to 5% failure rate

38 Combined contraceptive Patch Each patch delivers 150 micrograms of norelgestromin & 20micrograms of ethinyl oestrodiol daily Applied weekly for 3 weeks followed by a 7 day patch free interval. No current data on the use of the patch in women using liver enzyme inducing drugs such as ART

39 Progestogen only Pill (POP) Traditional POPs work by thickening cervical mucus Cerazette, containing desogestrel also works by inhibiting ovulation in most women

40 Progestogen-only injections - Depo Provera An aqueous suspension available in a pre-filled syringe Given by deep intramuscular injection into the gluteal region every 12 weeks

41 Subdermal implant - Implanon Etononorgestrel implant acts by preventing ovulation Contraceptive efficacy for 3 years Very effective. Failure rate < 0.1 in 100

42 Potential problem- Implanon/EFV use + =

43 IUS / Mirena A small, T-shaped, plastic contraceptive insert that is placed directly into the uterus and delivers hormone (levonorgestrel) locally to minimise side effects Used by only 1% of women in the UK and lasts for 5 years 20 µg daily dose of levonorgestrel 1 equivalent to 2 POPs per week 2

44 IUS Has progestogenic effect on the endometrium that prevents implantation+ cervical mucus Reduces menstrual blood> 90%, reduces the risk of transmission by reducing viral shedding

45 Available Options Daily Combined oral contraceptive Pill oestrogen (25-50 microgms)+ progesterone Progesterone only Pill (POP) Weekly Contraceptive patch 12 weekly Depo Provera injection 3 yearly Implanon contraceptive implant LARC 5 yearly 5 10 yrs Mirena intrauterine system IUS LARC Intrauterine Device -Copper T

46 Hormonal Contraception and decreased contraceptive efficacy with ART Hormonal Contraception and ART are metabolised by the same liver enzymes (cytochrome P450) Antiretrovirals are enzyme inducers and speed up the metabolism of hormonal contraceptives reduce the steroid hormone levels in the blood This applies to COC, POP and implant

47 However..Depo Provera & IUS No evidence that ARVs / liver enzyme inducers reduce the efficacy of progestogen-only injectables (including DPMA) or the levonorgestrel-releasing intrauterine system (IUS) No alteration in the standard dosage or frequency of injections is required.

48 Hormonal Contraception and decreased contraceptive efficacy with ART For women using the COC, some recommend prescribing 50 micrograms of oestrogen instead of the usual mcg of ethinyl oestrodiol. Enzyme inducing effect lasts for 4 weeks following cessation of the drug

49 ARV Contraceptive steroid level ARV level Pharmacokinetic COC-ARV drug interactions Protease Inhibitors Nelfinavir Ritonavir Lopinavir Atazanavir No data No data No data No data Amprenavir Saquinavir No change Non-nucleoside reverse transcriptase inhibitors Nevirapine Efavirenz Delavirdine No effect on progestogen May effect ethinyloestrodiol No Change No change No data

50 ART & contraception Oral DMPA Implanon EFV Barrier too No impact but levels vary so barrier too Not studied, exposure expected, cases of failure NVP Not sole method No impact OK Interaction unlikely but NR RPV No dose adjustment Likely fine but no data Likely fine but no data ETR No dose adjustment No dose adjustment No dose adjustment ATV/r DRV/r LPV/r fapv/r At least 30mcg EE. If prog other than norgestimate, NR (C) Oestrogen-based use alt/additional (no POP advice) Additional methods if oestrogen containing Non-hormonal methods recommended Not studied therefore NR Likely fine Likely fine Non-hormonal methods recommended Not studied therefore NR Interaction unlikely but NR Interaction unlikely but NR Non-hormonal methods recommended MVC No dose adjustment Likely fine Likely fine RAL No dose adjustment No dose adjustment No dose adjustment

51 No evidence of interactions with hormonal contraception Protease Inhibitors Indinavir Probably no clinically significant interaction Nucleoside reverse transcriptase inhibitors Abacavir Didanosine Emtricitabine Lamivudine Stavudine Tenofovir Zalcitabine Zidovudine

52 Copper IUDs Acts by preventing fertilisation and inhibiting implantation Effective for 5 to 10 years depending on the device

53 Copper IUDs No evidence of increased complications when compared to HIV negative women IUD use does not increase the risk of HIV acquisition IUD does not appear to increase shedding of HIV increased transmission A safe and effective method for women with HIV

54 Diaphragms and Caps Diaphragms cover the cervix and part of the vaginal wall Caps only cover the cervix Used with nonoxinol-9 Not appropriate for HIV positive woman or at significant risk of acquiring HIV

55 Depo Provera and bone density Depo Provera reversible loss in bone mineral density HIV infection - associated with reduced bone density Some ARTs can reduce bone density After discussion, women may opt for Depo Provera but consider a bone scan prior to initiation of the injection.

56 Hormonal Contraception and use of Antiretroviral therapy Answers Is there decreased contraceptive efficacy? Is there decreased efficacy of ART? Are there increased side effects related to either the hormonal contraception or the ART

57 Case review: Zara Opts for Depot injection on 3 monthly intervals when she will be collecting her ARVs Commenced on Atripla Before she leaves she is provided with this------

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59 Useful websites Date of prep: Jan Item code: UK/HIV/2012/0170a(1)

60 Thank you for listening

61 ARV-SPECIFIC DATA

62 Sexual and reproductive health survey of HIV positive women in Leicester To ascertain: Sexual activity Contraceptive and condom use Pregnancy plans To establish need for a dedicated SRH clinic at the site of HIV care

63 Results condom use 63% (72/114) currently sexually active Condom use: Always 74% Sometimes 19% Never 7% 88% (63/72) aware of partners status If status unknown: Always 71%

64 Contraceptive Method M. con F.con Pills Implant Depo IUS IUCD F.steri M.steri

65 Summary Good knowledge of benefits of HAART in pregnancy (50% unplanned pregnancy) High rate of sexual abstinence Good usage of LARC methods 16% vs 9% Sub-optimal condom use, not obtained from NHS providers A dedicated clinic likely to be well received